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Biomedical subjects

H L Davis

Publications and source records attributed to H L Davis.

At least 127 records · Page 7Linked to original sources
PubMed1978

Epileptiform seizures in domestic fowl. VII. Plasma phenytoin concentrations and anticonvulsant activity.

Acute dose-response studies with phenytoin were conducted to determine the relationship between plasma levels and anticonvulsant effect in epileptic chickens. Phenytoin produced statistically significant reductions in both the incidence and severity of seizures in photosensitive epileptic chickens when the plasma concentrations exceeded 8.15 +/- 0.89 microgram/ml. A high correlation exists between plasma phenytoin concentrations and both the reduction in incidence or severity of seizures. However, the appearance of plasma concentration dependent neurological toxicities resulted in a failure to achieve complete protection against intermittent photic stimulation induced seizures.

Animals↗
PubMed1978

Epileptiform seizures in domestic fowl. VIII. Anticonvulsant activity of primidone and its metabolites, phenobarbital and phenylethylmalonamide.

Primidone is an effective anticonvulsant against seizures induced in epileptic fowl by exposure to intermittent photic stimulation. Epileptic fowl metabolize primidone to phenobarbital. Pretreatment of epileptic fowl with SKF 525A to prevent the metabolism of primidone to phenobarbital indicated that primidone itself had anticonvulsant activity. Phenylethylmalonamide, a second metabolite of primidone, did not have anticonvulsant activity when administered at the same dose as primidone.

Animals↗
PubMed1978

Epileptiform seizures in domestic fowl. IX. Implications of the absence of anticonvulsant activity of ethosuximide in a pharmacological model of epilepsy.

Acute dose--response studies were conducted to determine if ethosuximide had anticonvulsant activity against seizures evoked by stroboscopic stimulation of epileptic fowl and to correlate the observed effects with the concentration of the drug in the plasma. Ethosuximide, in doses that produced mean plasma concentrations of 366 microgram/ml and signs of sedation, did not reduce seizure susceptibility. Twice daily administration of ethosuximide produced mean plasma concentrations of 430 microgram/ml after 36 h without affecting seizure susceptibility even in the presence of marked sedation. Previous studies have shown that epileptic fowl are sensitive to the anticonvulsant effects of phenobarbital, phenytoin, and primidone at plasma concentrations similar to those required in humans. Since ethosuximide has a high specificity against petit mal seizures in humans, the failure of ethosuximide to provide protection indicates that epileptic fowl represent a relatively specific pharmacological model for drugs effective against generalized tonic--clonic and focal cortical epilepsies in humans.

Animals↗
PubMed1978

Hormonal therapy of breast cancer: new approaches and concepts.

The most useful new hormonal therapy against estrogen receptor-containing metastatic breast cancer is the development of antiestrogenic agents such as nafoxidine and tamoxifen. Both of these drugs possess antitumor activity comparable to that of other additive hormonal agents, and they are better tolerated for lack of any serious toxicity. The clinical usefulness of antiprolactin drugs in breast cancer is at present limited. Adrenal suppression using aminoglutethimide has been shown to induce useful remissions. We discuss the implications of new treatment modalities for the future management of disseminated breast cancer.

Adrenalectomy↗
PubMed1978

Analysis of adjuvant therapy in large bowel cancer.

Since 1958 there has been intense efforts in adjuvant systemic therapy for colorectal cancer. Peri-operative chemotherapy with HN2, TSPA + FUDR produced no clear-cut prolongation of disease-free survival. Short-term (two courses) and long-term (18 months) therapy with 5-FU by the Veterans Administration surgical Adjuvant Group is reported to give marginal increases (7--9%) in survival at 5 years. These findings are confirmed by the COG study of prolonged 5-FU which shows prolongation of disease-free survival of borderline statistical significance for Dukes' C colon (P = 0.051) + rectum (P = 0.016). Short-term benefit to 18 months was conferred by prolonged 5-FU in the VASAG + COG studies, for patients who have had a palliative resection. Combination chemotherapy might be more active, but no results are available from the controlled trials utilizing 5-FU + MeCCNU or immunotherapy. Preoperative irradiation in the VASAG studies resulted in downstaging in terms of operative findings of lymph node involvement and was of survival benefit in those patients have an AP resection for cure or palliation of rectal cancer (P less than 0.02). More intensive preoperative radiation programs are ongoing, as well as postoperative radiation with and without chemotherapy. Further progress awaits the discovery of truly active chemotherapy programs, as well as better techniques of radiation enhancement.

Antineoplastic Agents↗
PubMed1977

Hemangiopericytoma of the bladder after polyvinyl alcohol exposure.

A patient with hemangiopericytoma of the bladder following intensive exposure to polyvinyl alcohol is reported. Some early studies on polymer carcinogenesis are reviewed and recent work on vinyl chloride as a mutagen and potent carcinogen is cited. The need for epidemiologic and animal studies of other monomers is presented.

Adult↗
PubMed1977

Review of local soft tissue recurrence of breast cancer irradiated with and without actinomycin-D.

Between 1962 and 1973, regionally recurrent breast cancer was treated in 156 patients by irradiation alone or irradiation with concurrent actinomycin-D. Thirty-two patients were entered into a randomized trial, and 124 patients were retrospectively reviewed. Local control with irradiation alone was achieved in 48 of 80 patients (60%) and in 60 of 76 patients (79%) treated with irradiation and actinomycin-D (p less than .05). Results were remarkably similar in the randomized and retrospective series.

Breast Neoplasms↗
PubMed1977

Epileptiform seizures in domestic fowl. VI. Plasma phenobarbital concentrations and anticonvulsant activity.

The relationship between plasma phenobarbital concentrations and anticonvulsant activity was determined against seizures induced in epileptic chickens by intermittent photic stimulation (IPS). Intraperitoneally administered phenobarbital produced a plasma-concentration-dependent reduction in both the incidence and severity of seizures. Complete protection against IPS-induced seizures was observed for a period of 6 h after acute phenobarbital administration during which the mean plasma phenobarbital concentrations were between 16.2 +/- 0.91 and 13.6 +/- 1.0 microgram/lm. Plasma phenobarbital concentrations below 3.6 +/- 0.06 microgram/ml had no measurable effect.

Animals↗
PubMed1977

Stage III ovarian carcinoma: treatment and results. Comparison of multiple drugs, a single drug, and irradiation.

Multiple drugs, a single drug, and irradiation were compared in patients with Stage III ovarian carcinoma. The results were categorized as "favorable" [pelvic mass less than 8 cm and/or upper abdominal tumor nodule(s) less than 2 cm] or "unfavorable" (more massive disease). A total of 62 patients are reviewed of whom 25 had irradiation and 37 had chemotherapy. It was found that patients with slight residual disease after celiotomy did equally well with either irradiation or chemotherapy, but survival was improved using a combination of both. Use of 5 drugs did not significantly improve survival beyond that obtained with a single drug.

Drug Therapy, Combination↗
PubMed1977

Current cooperative clinical trials in the non-Hodgkin's lymphomas.

Current cooperative group trails in non-Hodgkin's lymphoma have been analyzed for their overall methods and strategies. There has been more frequent application of staging procedures and individualization of protocols for favorable and unfavorable histologies according to the Rappaport classification. Early-stage protocols are evaluating the extent of radiotherapy and the need for chemotherapy as maintenance. In later stages the incorporation of new agents in induction regimens, use of cycle-active agents, development of non-cross-resistant combinations, and use of radiation in bulk disease are being examined. In childhood lymphoma, strategies using both leukemia- or lymphoma-type approaches are being tested. Cooperative group trials should also serve as an extensive repository of data on late effects of treatment and on alterations of the course of the disease for future analysis.

Adult↗
PubMed1977

Whatever happened to NSC--? An analysis of clinical results of discontinued anticancer agents.

Twenty-six investigational anticancer drugs formerly supplied by the National Cancer Institute are no longer available due to the lack of requests for their use in clinical trials. This report examines the data on these drugs to determine how well they were clinically evaluated. Generally, the studies are incomplete, and 34% of the compounds have not been studied beyond phase I trials. Clinical pharmacology data were not obtained for most of the drugs. In addition, the information available for drugs that did undergo phase II trials is grossly inadequate and does not permit a confident decision to withdraw them from investigational use. Instances of "hints" of activity and interesting drug properties are cited to stimulate further study. Finally, a list of compounds scheduled for future termination is given within the framework of this analysis to provoke thought toward obtaining more phase II data before these drugs fall into disuse.

Alkylating Agents↗
PubMed1976

Improved theophylline serum analysis by an appropriate internal standard for gas chromatography.

A gas chromatographic method is presented for the measurement of theophylline in serum. To serum samples containing the drug the internal standard, 3-isobutyl-l-methylxanthine, was added and the serum was saturated with ammonium carbonate. A mixture of isopropanol-chloroform (5:95) was used for extraction. The organic phase was filtered and evaporated. The residue, dissolved in chloroform, was extracted with sodium hydroxide. The basic solution was acidified, washed with hexane and reextracted with isopropanol-chloroform. The organic phase was dried with anhydrous sodium sulphate before evaporation. The sample was derivatized with n-Butyl-8 reagent. 85% of theophylline was recovered by extraction. 3-Isobutyl-l-methylxanthine was recovered with the same efficiency as theophylline and gas chromatographed well. The standard curve was linear between 1.0 and 50.0 mug/ml theophylline. No interference was encountered from normal serum constituents or methylxanthines such as caffeine, theobromine, or 3-methylxanthine. Serum samples were stared in the refrigerator for two weeks without significant loss of drug. The precision and accuracy of the method were good.

Chromatography, Gas↗
PubMed1976

Further clinical studies with megestrol acetate in advanced breast cancer.

A previous study showed activity of megestrol acetate in advanced breast cancer; as a result the study was expanded. Of 101 patients treated with this compound, 26 (26%) met our criteria of improvement. The drug was well tolerated and produced no toxicity and, as opposed to androgens and estrogens, no endocrine effects were observed. Prior hormonal or cytotoxic compounds, including alkylating agents, did not appear to reduce the subsequent responsiveness to this potent progestational compound. We now include it, often as the initial hormonal trial in postmenopausal patients, in our sequential treatment of disseminated breast cancer because of its favorable therapeutic ratio.

Breast Neoplasms↗
PubMed1976

The necessity of drug level monitoring in anticonvulsant drug therapy.

A survey of 'steady-state' serum levels of anticonvulsant drugs from 221 epileptic patients at a university hospital was conducted. Serum concentrations of phenobarbital, primidone, and diphenylhydantoin were determined by a gas chromatographic method. Sixty-five percent (130) of the patients receiving diphenylhydantoin had levels below the therapeutic range of 10-20mug/ml. Subtherapeutic levels appear to be due to inadequate dosage adjustment. Only 25% (33) of the patients receiving phenobarbital had levels below the therapeutic range. Serum levels of diphenylhydantoin or phenobarbital could not be predicted from dosage. Most patients received two or more drugs. Over 10% of the patients had potentially toxic levels of anticonvulsant drugs. High levels of diphenylhydantoin were easily recognized clinically but high levels of phenobarbital were not.

Body Weight↗
PubMed1976

Combined radiation therapy and 5-fluorouracil for advanced squamous cell carcinoma of the oral cavity and oropharynx: a randomized study.

In 1961, a randomized study was begun at the University of Wisconsin Medical Center in which the treatment of advanced squamous cell carcinoma of the head and neck with radiation therapy was compared with combined treatment with radiation therapy and 5-Fluorouracil. One hundred and thirty-six patients with primary lesions in the oral cavity, the base of the tongue, and the oropharynx were analyzed. Both local control and survival were better in the combined treatment group than in the group with radiation therapy alone. However, in only the oral cavity patient population was the difference statistically significant. Both acute and late complications were also increased in this group of patients who received combined treatment.

Carcinoma, Squamous Cell↗
PubMed1976

Multimodal surgical adjuvant therapy for a broad spectrum of tumors in humans.?

Co-operative investigation of clinical therapy for cancer is used to test hypotheses developed in single institutions and in animal research laboratories. The present studies in a large co-operative organization, the Central Oncology Group, are being conducted in seven major solid tumors in adults; in these studies patients with a poor surgical prognosis are being treated with preoperative or postoperative chemotherapy, preoperative radiotion therapy of these modalities. Results of studies currently underway or recently completed in 1,278 patients are summarized. In most instances, the research has demonstrated little or no apparent improvement in the disease free interval or the survival time from adjuvant therapy, although only on of the studies has been completed and fully evaluated thus far. In carcinoma of the colon and rectum and melanoma, mild toxicity from drug therapy has been associated with statistically significant improvement in survival times. These studies have produced base line information on disease free intervals, time to progression and survival time in patients with cancer who are seen in the participating institutions. These observations are expected to useful in the planning of future adjuvant studies.

Adult↗